Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07D—HETEROCYCLIC COMPOUNDS
  • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
  • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
  • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
  • C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
  • C07D211/60—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
  • C07D211/62—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4
  • C07D211/64—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals attached in position 4 having an aryl radical as the second substituent in position 4

Definitions

• compositions preferably in dosage unit form, containing 1-(3-cyano-3,3- diphenylpropyl)-4-phenylisonipecotic acid or a therapeutically active acid addition salt thereof as the active ingredient. It has been found that 1-(3-cyano-3,3-diphenylpropyl) 4 -phenylisonipecotic acid possesses marked antidiarrheal and analgesic activities.
• 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid or salt thereof is combined in intimate admixture with a pharmaceutical carrier, which carrier may take a wide variety of forms depending on the form of preparation desired for administration, i.e., oral or parenteral.
• any of the usual pharmaceutical media may be employed, such as, for example, Water, glycols, oils, alcohols and the like in the case of oral liquid preparations such as suspensions, elixirs and solutions; or solid carriers such as starches, sugars, kaolin, lubricants, binders, disintegrating agents and the like in the case of powders, capsules and tablets. Because of their case in administration, tablets and capsules represent the most advantageous oral dosage form, in which case solid pharmaceutical carriers are obviously employed.
• the carrier will usually comprise sterile water, at least in large part, though other ingredients, for example, to aid solubility, may be included.
• Injectable solutions for example, may be prepared in which the carrier comprises saline solution, glucose solution or a mixture of saline and glucose solution.
• Injectable suspensions may also be prepared in which case appropriate liquid carriers, suspending agents and the like may be employed.
• the compositions per dosage unit e.g., tablet, capsule, injection, teaspoonful, powder and the like, will contain at least from about 0.1 mg. to about 25 mg. of the active ingredient.
• the preferred compound herein, 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid hydrochloride is found to have an LED of 0.02 mg./kg. orally.
• the subject compounds In addition to anti-diarrheal activity, the subject compounds also possess morphine-like analgesic activity, as demonstrated in the rat tail withdrawal test described in Arzneistoff-Forschung 13, 502 (1963). According to this procedure, the LED of l-(3-cyano-3,3-diphenylpropyl)- 4-phenylisonipecotic acid hydrochloride is about 2.5 mg./ kg. orally.
• the precipitated product is filtered off, washed with water, dried, dissolved in 50 parts of 0.4 N potassium hydroxide and precipitated again with glacial acetic acid.
• the crude free base is filtered off and dissolved in a mixture of 2-propanol and chloroform and gaseous hydrogen chloride is introduced into the solution. The whole is filtered and the filtrate is evaporated. The residue is mixed with benzene and the latter is evaporated again.
• the residue is recrystallized from 2-propanol, yielding l-(3-cyano- 3,3-diphenylpropy1)-4-phenylisonipecotic acid hydrochloride.
• EXAMPLE II 10,000 hard gelatin capsules, each containing as the active ingredient (A.I.) 2.5 milligrams of l-(3-cyano-3,3- diphenylpropyl)-4-phenylisonipecotic acid hydrochloride, are prepared from the following formulation:
• EXAMPLE IIITables 5,000 compressed tablets, each containing as the active ingredient 5 milligrams of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid hydrochloride are prepared from the following formulation:
• the finely powdered ingredients are mixed well and granulated with 10% starch paste.
• the granulation is dried and compressed into tablets using starch as a disintegrant and calcium stearate as a lubricant.
• EXAMPLE lVInjectable The following formulation provides 1 liter of a parenteral suspension comprising 1 mg. of l-(3-cyano-3,3-
• EXAMPLE Vral suspension The following formulation provides liters of an oral suspension comprising 0.5 mg. of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid hydrochloride as the Dissolve the parabens in the propylene glycol and add this solution to a solution of the sodium cyclamate, sodium saccharin and sucrose in half the water. Suspend the bentonite in hot (about '85 C.) water and stir for 60 minutes. Add the bentonite solution to the former solution.
• a pharmaceutical composition in dosage unit form comprising an effective amount to inhibit gastrointestinal propulsion of a member selected from the group consisting of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid and the therapeutically active acid addition salts thereof as an active ingredient admixed with a pharmaceutical carrier.
• a pharmaceutical composition in dosage unit form comprising per dosage unit from about 0.1 toabout 25 mg. of a member selected from the group consisting of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid and the therapeutically active acid addition salts thereof as an active ingredient in admixture with a solid pharmaceutical carrier.
• Claim 2 wherein said active ingredient is 1 (3-cyano 3,3-diphenylpropyl)-4-phenylisonipecotic acid hydrochloride.
• a liquid pharmaceutical composition comprising from about 0.1 mg. to about 25 mg. per dosage unit of a member selected from the group consisting of 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid and the therapeutically active acid addition salts thereof as an active ingredient in a liquid medium suitable for oral administration.
• An injectable pharmaceutical composition comprising from about 0.1 to 25 mg. per dosage unit of a member selected from the group consisting of 1-(3-cyano-3,3- diphenylpropyl)-4-phenylisonipecotic acid and the. therapeutically active acid addition salts thereof as an active ingredient in a liquid medium suitable for parenteral administration.
• the method of inhibiting gastro-intestin'al propulsion which comprises internally administering to a'warm blooded animal a pharmaceutical composition in dosage unit form comprising per dosage unit from about 0.1 to about 25 mg. of a member selected from the group consisting of l-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid and the therapeutically active acid addition salts thereof as an active ingredient in admixture with a pharmaceutical carrier.
• said active ingredient is 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotic acid hydrochloride.

Landscapes

• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Medicinal Preparation (AREA)
• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
• Hydrogenated Pyridines (AREA)
• Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
• Investigating Or Analyzing Non-Biological Materials By The Use Of Chemical Means (AREA)

Applications Claiming Priority (1)

Publications (1)

Family

ID=25097879

Family Applications (1)

Country Status (21)

• 1968
  • 1968-11-04 US US773324A patent/US3646207A/en not_active Expired - Lifetime
• 1969
  • 1969-10-12 IL IL33167A patent/IL33167A/xx unknown
  • 1969-10-17 IE IE1427/69A patent/IE33602B1/xx unknown
  • 1969-10-28 CH CH1606069A patent/CH517742A/fr not_active IP Right Cessation
  • 1969-10-31 SU SU1373679A patent/SU489324A3/ru active
  • 1969-10-31 ES ES373101A patent/ES373101A1/es not_active Expired
  • 1969-10-31 GB GB1234359D patent/GB1234359A/en not_active Expired
  • 1969-10-31 LU LU59733D patent/LU59733A1/xx unknown
  • 1969-11-03 FR FR696937762A patent/FR2022531B1/fr not_active Expired
  • 1969-11-03 PL PL1969136662A patent/PL80327B1/pl unknown
  • 1969-11-03 BR BR213868/69A patent/BR6913868D0/pt unknown
  • 1969-11-03 YU YU2737/69A patent/YU34188B/xx unknown
  • 1969-11-03 NO NO4358/69A patent/NO133803C/no unknown
  • 1969-11-03 SE SE15022/69A patent/SE354067B/xx unknown
  • 1969-11-03 BE BE741155D patent/BE741155A/xx unknown
  • 1969-11-04 ZA ZA697742A patent/ZA697742B/xx unknown
  • 1969-11-04 NL NL696916611A patent/NL146380B/xx not_active IP Right Cessation
  • 1969-11-04 AT AT1034769A patent/AT293387B/de active
  • 1969-11-04 RO RO61465A patent/RO57886A/ro unknown
  • 1969-11-04 DK DK580369AA patent/DK129124B/da not_active IP Right Cessation
  • 1969-11-04 CS CS727969A patent/CS156461B2/cs unknown

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